chr1-83870002-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024686.6(TTLL7):​c.2624G>A​(p.Arg875His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,590,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

TTLL7
NM_024686.6 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.41

Publications

0 publications found
Variant links:
Genes affected
TTLL7 (HGNC:26242): (tubulin tyrosine ligase like 7) Enables alpha-tubulin binding activity; beta-tubulin binding activity; and tubulin-glutamic acid ligase activity. Involved in protein polyglutamylation. Predicted to be located in 9+0 non-motile cilium and ciliary basal body. Predicted to be active in cilium. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.094806135).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TTLL7NM_024686.6 linkc.2624G>A p.Arg875His missense_variant Exon 21 of 21 ENST00000260505.13 NP_078962.4 Q6ZT98-1
TTLL7NM_001350214.2 linkc.2624G>A p.Arg875His missense_variant Exon 22 of 22 NP_001337143.1
TTLL7NM_001350215.2 linkc.2543G>A p.Arg848His missense_variant Exon 20 of 20 NP_001337144.1
TTLL7XM_047430691.1 linkc.1889G>A p.Arg630His missense_variant Exon 15 of 15 XP_047286647.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TTLL7ENST00000260505.13 linkc.2624G>A p.Arg875His missense_variant Exon 21 of 21 2 NM_024686.6 ENSP00000260505.8 Q6ZT98-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000131
AC:
3
AN:
228726
AF XY:
0.0000241
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000188
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000174
AC:
25
AN:
1438384
Hom.:
0
Cov.:
30
AF XY:
0.0000196
AC XY:
14
AN XY:
715082
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32028
American (AMR)
AF:
0.00
AC:
0
AN:
39194
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25690
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37968
South Asian (SAS)
AF:
0.0000368
AC:
3
AN:
81544
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53240
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5724
European-Non Finnish (NFE)
AF:
0.0000181
AC:
20
AN:
1103558
Other (OTH)
AF:
0.0000336
AC:
2
AN:
59438
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.443
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152134
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74312
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41424
American (AMR)
AF:
0.0000655
AC:
1
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5198
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10596
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68030
Other (OTH)
AF:
0.00
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.2624G>A (p.R875H) alteration is located in exon 21 (coding exon 20) of the TTLL7 gene. This alteration results from a G to A substitution at nucleotide position 2624, causing the arginine (R) at amino acid position 875 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.046
T
Eigen
Benign
-0.14
Eigen_PC
Benign
0.039
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.0051
T
MetaRNN
Benign
0.095
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.95
L
PhyloP100
2.4
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.034
Sift
Benign
0.084
T
Sift4G
Benign
0.12
T
Polyphen
0.032
B
Vest4
0.14
MutPred
0.38
Loss of methylation at R875 (P = 0.0471);
MVP
0.21
MPC
0.64
ClinPred
0.23
T
GERP RS
3.7
Varity_R
0.092
gMVP
0.62
Mutation Taster
=90/10
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs200003317; hg19: chr1-84335685; COSMIC: COSV53084024; API